Design, synthesis and structure-activity relationship study of piperazinone-containing thieno[3,2-d]pyrimidine derivatives as new PI3Kδ inhibitors

[Display omitted] Two classes of piperazinone-containing thieno[3,2-d]pyrimidines were designed and synthesized as new PI3Kδ inhibitors in this study. Detailed SAR study with respect to the piperazinone substituents at the 6-position of thieno[3,2-d]pyrimidine core demonstrated that piperazinone-con...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2020-10, Vol.30 (20), p.127479-127479, Article 127479
Hauptverfasser: Wang, Ning-Yu, Zuo, Wei-Qiong, Hu, Rong, Wang, Wan-Li, Zhu, Yong-Xia, Xu, Ying, Yu, Luo-Ting, Liu, Zhi-Hao
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Sprache:eng
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Zusammenfassung:[Display omitted] Two classes of piperazinone-containing thieno[3,2-d]pyrimidines were designed and synthesized as new PI3Kδ inhibitors in this study. Detailed SAR study with respect to the piperazinone substituents at the 6-position of thieno[3,2-d]pyrimidine core demonstrated that piperazinone-containing thieno[3,2-d]pyrimidines would be more potent and selective for PI3Kδ than their piperazine counterparts, which led to the discovery of several potent PI3Kδ inhibitors with comparable or better antiproliferative activity against a panel of non-Hodgkin lymphoma (NHL) cell lines as compared with idelalisib. Our study will promote the development of new PI3Kδ inhibitors based on piperazinone-containing thieno[3,2-d]pyrimidine scaffold.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2020.127479